A growth hormone-releasing hormone (GHRH)-secreting pancreatic tumor in a 36-year-old man, who had typical, familial, multiple endocrine neoplasia (MEN) type I with hyperparathyroidism and acromegaly, is described. The resected tumor, weighing 30 g, showed unusual histological features characterized by a meningioma-like arrangement of crescent-shaped cells and contained many cells that reacted with C-terminal specific antibody to GHRH-44 and a few somatostatin-immunoreactive (IR) and calcitonin-IR cells, but no GH-IR cells. A high concentration of IR-GHRH (9.8-13.2 micrograms/g wet weight tissue) with the full molecular size of GHRH-44 was detected in a tumor extract. Electron immunocytochemical study by the protein A-gold method revealed GHRH-IR granules with a mean diameter of 147 nm. After removal of the tumor, the plasma IR-GHRH level became normal (decreasing from 299 to 16.1 pg/ml) and the plasma IR-GH level also decreased, but still remained slightly high (decreasing from 42.4 to 9.6 ng/ml), suggesting the presence of an adenomatous lesion in the hypophysis.